We propose to create a deletion in the mouse genome for the mouse analogue of the human met oncogene. Mice homozygous for the deletion would be a possible model for the human disorder cystic fibrosis (CF). It has recently been found that met, which maps to human chromosome 7, might even be the CF gene or is very closely linked to cystic fibrosis (less than 0.7 cM). Since there is a high degree of conservation of linkage between mouse and man, a radiation-induced deletion of the met locus in mice may well also remove the mouse analogue of the CF gene. We will search for such a deletion by screening DNA of F1 mice where one of the parents has been irradiated as part of an ongoing mutation project at Research Triangle Institute. This is a high risk project because (1) the screening of progeny from irradiated animals will not be efficient unless we are able to identify a restriction fragment length polymorphism between the parental strains whose F1 progeny we will be screening, (2) the number of progeny mice which will need to be screened is large, (3) the met-"CF" portion of the mouse genome may include genes necessary for embryonic development such that the homozygotes for the deletion would not survive long enough to be useful, and (4) the linkage may not be maintained. Nonetheless, we believe that the immense value of a murine model for treatment efforts, including gene therapy, warrants taking the risk.